BIO-INFORMATICS DEVELOPMENTS IN BIOTECHNOLOGY IN INDIA
BIO-INFORMATICS & DEVELOPMENTS of BIOTECHNOLOGY
BIO-INFORMATICS DEVELOPMENTS IN BIOTECHNOLOGY IN INDIA
Bioinformatics is the application of information technology to the field of molecular biology. The term bioinformatics was coined by Paulien Hogeweg in 1978 for the study of informatics processes in biotic systems. Bioinformatics nowadays entails the creation and advancement of databases, algorithms, computational and statistical techniques, and theory to solve formal and practical problems arising from the management and analysis of biological data. Over the past few decades rapid developments in genomic and other molecular research technologies combined developments in information technologies have combined to produce a tremendous amount of information related to molecular biology. It is the name given to these mathematical and computing approaches used to glean understanding of biological processes. Common activities in Bioinformatics include mapping and analyzing DNA and protein sequences, aligning different DNA and protein sequences to compare them and creating and viewing 3-D models of protein structures. Bioinformatics is that branch of life science, which deals with the study of application of information technology to the field of molecular biology.
The primary goal of bioinformatics is to increase our understanding of biological processes. What set it apart from other approaches, however, is its focus on developing and applying computationally intensive techniques (e.g., data mining, and machine learning algorithms) to achieve this goal. Major research efforts in the field include sequence alignment, gene finding, genome assembly, protein structure alignment, protein structure prediction, prediction of gene expression and protein-protein interactions, and the modeling of evolution.
Bioinformatics was applied in the creation and maintenance of a database to store biological information at the beginning of the “genomic revolution”, such as nucleotide and amino acid sequences. Development of this type of database involved not only design issues but the development of complex interfaces whereby researchers could both access existing data as well as submit new or revised data.
DEVELOPMENTS IN BIOTECHNOLOGY IN INDIA
The setting up of a separate Department of Biotechnology (DBT), under the Ministry of Science and Technology in 1986 gave a new impetus to the development of the field of modern biology and biotechnology in India. The department has made significant achievements in the growth and application of biotechnology in the broad areas of agriculture, health care, animal sciences, environment, and industry. Autonomous institutions like Institute of Bioresources and Sustainable Development (IBSD), Imphal, Manipur. Institute of Life Sciences, Bhuvanesva a National Institute Of Immunology, New Delhi., National Institute for Plant Genome Research (NIPGR), JNU, New Delhi., National Brain Research Centre (NBRC), Gurgaon., National Centre for Cell Sciences, Pune, Rajiv Gandhi Centre for Biotechnology and public sector undertakings like Bharat Immunologicals & Biologicals Corporation Limited, Bulandshahar., Indian Vaccines Corporation Limited, Gurgaon are pioneering the research and development in the field of biotechnology.
Initiatives have been taken to promote transgenic research in plants with emphasis on pest and disease resistance, nutritional quality, silk-worm genome analysis, molecular biology of human genetic disorders, brain research, plant genome research, development, validation and commercialisation of diagnostic kits and vaccines for communicable diseases, food biotechnology, biodiversity conservation and bioprospecting, setting up of micropropagation parks and biotechnology based development for SC/ST, rural areas, women and for different States.
Necessary guidelines for transgenic plants, recombinant vaccines and drugs have also been evolved. A strong base of indigenous capabilities has been created. The field of biotechnology both for new innovations and applications would form a major research and commercial endeavor for socio-economic development in the next.
(a) In the Area of Food
At Trombay, BARC the research in bio-sciences is directed towards evolving high yielding food crops, delaying or preventing post-harvest losses by increasing shelf life.
A programme on nutrition biofortification, incorporation of quality traits like essential amino acids, mono unsaturated fatty acids and iron and zinc in our staple food crops. Work has been initiated on the structural and functional economics of tomato, and functional geomics of rice, sugarcane and shrimp. Characterisation and validation of mangrove genes in transgenic rice systems for abiotic stress tolerance. Programmes are also being generated for the development of high throughput robust markers in cropslike Indian pulses, oilseeds and fodder corps. Several social concerns that need to be addressed in order to ensure that the fruits of biotechnology reach all strata of the society.
The high-quality chromosome-anchored sequence generated by the International Rice Genome Sequencing Project (IRGSP) which had a participation from India was published which represents the most accurate and complete sequence from a higher organism. By generating more than half-a-million individual sequences, Indian scientists assembled 16.5 million bases of chromosome 11 for 1443 genes. Blast resistance gene pikh (t) in the rice line Tetep is being targeted for development of high resolution mapping and cloning of suitable genes to develop durable blast resistant cultivars for the north-western Himalayan region of India.
The mustard hybrid DMH-11 is being tested in multi-site trials with permission of RCGM at the ICAR’s National Research Centre on Rapeseed Mustard, Bharatpur at 11 locations. In a network project on salinity and dehydration stress tolerance in rice, for cloning of stress responsive genes, a total of seven subtractive cDNA libraries were made. All 4000 putative ESTs/ cDNA clones from Pokkali were obtained from these libraries, at ICGEB and around 11800 clones have been sequenced. In cotton project, a few fines showed expression levels of Cry 1A(c) constructs has been continued and these lines are being assessed for their expression levels.
For bread wheat improvement, the chromosome elimination technique was used following wheat x maize system for the development of doubled haploid (DH) populations. Under network project on wheat quality breeding through the use of molecular marker technology, a number of marker-trait associations have been detected by single marker analysis both for bread making quality and seed traits using 4 mapping populations. Efforts are also being made to bring resistance against Karnal Bunt in cultivated wheat varieties. Attempts are also being made to develop species-specific molecular markers for characterization of different species of Saccharum and their hybrids.
(b) In the Area of Health
This area of research has reported many significant leads such as: a substance isolated from the leaf of the betel plant (piper betel) which is able to induce death of cancer cells in chronic myeloid leukemia (CMK) – a type of cancer that attacks white blood cells; development of process for the Oral Delivery of Insulin and Hepatitis B vaccine. A comparative economics method has been developed which helps to identify non active site (structural determinants) of proteins as drug targets. A crude extract, obtained by the enzyme-acid hydrolysing process from a marine organism (mussel) which shows initially a potent anti-malarial activity, a least when examined for in vitro cultures of Plasmodium falciparum in human erythrocytes has been reported.
Another significant lead has been the development of Gelatin micro spheres and evaluation of SSD loaded Collagen membranes for wound healing. It was found that wound healing is accelerated by – 60 per cent. Isolation of a bacterium (Bacillus sp.) that lives under extreme environmental condition and produces an aspartic protease inhabiter (ATBI) has been reported.
National Jai Vigyan and Mission Mode Programme – on S & T for New Generation Vaccines: The Department Has given major emphasis towards development of new generation vaccines using novel strategies for developing new and improved vaccines for major diseases prevalent in India this includes development of safe and efficiacious vaccine for Cholera, Rabies, JE, Tuberculosis, Malaria and HIV/AIDS. They are at various clinical and pre-clinical stages. The vaccine based on VA1.3 strain of V. cholerae has completed phase- I & II clinical trials in adults. The results revealed that the vaccine is safe and comparable to the best vaccine available in the international market. The first DNA based Rabies vaccine for animals is undergoing clinical trials at five centres. Two recombinant candidate antigens of P.falciparum and P.vivax have been produced under GLP conditions at ICGEB, New Delhi and produced clinical grade material under cGMP conditions at M/s BBIL, Hyderabad. Necessary steps have been initiated to conduct pre-clinical trial. The vaccine for JE is under pre-clinical studies.
New Millenium Indian Technology Leadership Initiative (NMITLI): NMITLI is able to create an unique brand for itself by flagging some S&T success which include: (I) development of formulations: one each for psoriasis, diabetes, arthritis and hepatic disorders following ‘Reverse Pharmacology’ approach – wherein modem science inputs are provided to age old traditional medicine knowledge to develop modem medicine.
The approach provides unique advantage in terms of reduced cost and time for drug developments and ultimately lower cost to the patient; (II) Lysostaphin – a novel biotherapeutic molecule for Staphylococcus infections – for which an Investigational New Drugs (IND) application has been cleared. The formulation will now be taken for Phase-I clinical studies; (III) advanced bio-informatics software such as BioSuite, BioCluster and Darshee. This area would enable India to become a global player in the area of bioinformatics; and
At BARC Trombay, developing modalities for low dose cancer radiotherapy and employing molecular and isotope techniques in basic biology for disease diagnosis and fingerprinting of individuals and population.
The National Centre for Biological Sciences of TIFR at Bangalore has been working on research initiatives in the frontline areas of modern biology. The Saha Institute of Nuclear Physics, Kolkata is engaged in research elucidating the structure function correlation of biomolecules at the cellular and molecular level. Towards this end the department is paying special attention to provide chose-effective and safe products. Major emphasis has been laid towards development of newer vaccines, diagnostics for the major infectious and chronic diseases and the lifestyle disorders. Three new Task Forces have been commissioned to develop and monitor programmes in areas of vaccines and diagnostics; infectious disease biology and chronic diseases biology with the involvement of basic and applied research scientists, clinicians and industry representatives.
A Medical Biotechnology Development Board has also been set up to provide continuous guidance and support towards generation of new ideas and areas for future research, address policy matters and closer interactions with the Task Forces. More than 70 new projects were implemented in various areas of medical biotechnology. A MOU has been signed between DBT and ICMR to pursue some of the biomedical research programmes jointly and priorities have been laid on HIV/AIDS research and microbicide development. Efforts have been initiated to develop a tetravalent dengue vaccine candidate. An indigenous rapid diagnostic test system (SIGNALKA), developed by AIIMS. New Delhi has been commercially launched. A PCR based detection system has been developed for SARS.
Biotech Facilities and Programme Support: Major support has been provided at universities viz., the transmission electron microscopy at Banaras Hindu University, Varanasi and the automated DNA sequencing facility at the Delhi University. The other facilities are-confocal microscopy facility at the Institute of Life Sciences, Bhubaneswar; augmentation of phytotron803 Scientific and Technological Developments containment facility at Indian Agricultural Research Institute, New Delhi; clinical proteomics and the flowcytometry facility at the All India Institute of Medial Science, New Delhi.
India has initiated a programme to augment and strengthen institutional research capacity in areas of biotechnology through support for establishment of Centres of Excellence. Five centres of excellence have been supported in areas of cancer biology and therapeutics; industrially important non-conventional yeasts; developing drought tolerant crop varieties; and The support for national facility for virus diagnosis and quality control of tissue culture raised plants and micro propagation for resource and technology development at the Energy and Resource Institute, New Delhi and National Chemical Laboratory, Pune, was continued.
Biofertilisers are considered to be an important eco-friendly alternative source of plant nutrition. Cyanobacterial strain Anabaena transformations for het R and groESL, genes under psbA1 promoter has been obtained and further studies are in progress. The technique of inter-and intraspecies hyphal fusion and fusant sportulation of AM fungi in vitro has been successfully standardized. An Azotobacter chroococcum strain has been transformed with cloned E. coli gluccose dehydrogenase (gdh) gene using Azotobacter specific promoters. Moreover, one Tn5 mutant of dctA gene has been obtained and characterised. Success was achieved in creating genetically modified strains Azospirillum for IAA biosynthesis and enhanced plant growth promoting activity. Endophytic mycorrhiza has been isolated from several orchid species/hybrids and study on the effect of these mycorrhizal fungi on symbiotic germination and growth of the selected orchids is in progress.
The benefit of Mycorrhizal inoculation in terms of enhanced plant growth, P-nutrition and soil friosture stress rolerance has been observed in actual field conditions of the citrus fruit plantation. The mass production of Mycorrhiza technology package has been transferred to two more industries for commercial production.
(d) Biopesticides and Crop Management
It is directed towards the management of pests, diseases and weeds of economically important crops as well as development of commercially viable mass production technologies. Formulations were prepared and tested against viral and fungal infections in vegetable crops and betel winer from the isolates of Trictoderma, Psuedomonas Bacillus sp. Steinernema carpocapsae was found to be effective as a biological control agent for pest management. Root extracts of Linostoma decundrum and leaves of Clerodendron inerme showed acaricidal, anti-ovipo-sitional and ovicidal properties against common tea pest. Bioefficacy of two new heat tolerant Steinernema seemae and Steinernema massodi was found to infect and kill pupae of H. armigera. For management of Parthenium, a biopeesticide product from Trichoderma viridi as 1.15 per cent wettable powder was registered. A draft report on market survey on biopesticide covering region wise requirement of biopesticides based on agricultural crops, their pest profile and area covered, etc., has been developed.
(e) Medicinal and Aromatic Plants
Four gene banks have been further strengthened with respect to conservation and characterisation of more number of geermplasm accessions. Preliminary success was obtained in cryopreservation of Allium chinesis, A. tuberosum and Bacopa monnieri. Spatially explicit map has been developed for Nothapadytes nimmoniana and other related species in Western Ghats. A patent has been field for a method of podophyllotoxin production in high yielding cell lines of Podophyllum hexandrum. Cell suspension raised from leaf and hairy root derived callus of Hyoscyamus muticus have been scaled-up in 15- litre bioreactor. Bioactive agents from Ocimum sanctum and Evolvulus alsinoides responsible for adaptogenic and immunomodulatory activities has been identified.
Work has been initiated to develop a standardized herbal formulation based on the lead obtained in Oxalis corniculata having anti-Entamoeba histolytica activity. Work has been carried out on cloning and expression of gene encoding hypoglycemic protein of Momordica charantia. A gene for operoxidase enzyme acting in the dimerisation step leading to the production of vinblastine in Catharanthus roseus has been characterised. A HPLC method was established to identify and quantitative the methoxybenzoates from the root organs of Hemidesmus indicus.
(f) Aquaculture and Marine Biotechnology
Efforts continues on enhancing productivity, searching for useful biomolecules from the sea, diagnostics and vaccine development, cell culture, bioremediation, molecular signaling in fish spawning and water quality management in aquaculture. An alkaline protease gene was cloned and protocol standardised for bioprocess and production of alkaline protease. Screening of marine organisms was undertaken for biologically active secondary metabolities as antibacterial, anti-malarial and anti-cancer agents. Production, purification and antimicrobial activity of biosurfactant(s) were studied using marine waters. Studied were undertaken on over expression of engineered SOD enzyme in marine cyanobacteria for bioremediation. A RapiDot Kit has been developed for detection of while spot shrimp virus. Programme support in marine biotechnology was provided to Cochin University of Science and Technology and the Fisheries College, Mangalore to work on development of disease resistant varieties, fast growing brood stocks, larval survival and molecular biology and to provide education, training, technology development and demonstration. A new network project on shrimp genomics covering brackish water species and freshwater prawn species has been initiated to study comparative and functional genomics related m g disease resistance, reproductive and larval development.
A road-map for seribiotechnology research has been prepared in collaboration with the Central Silk Board. A noval lysozyme-like protein has been identified in Bombyx mori and Antheraea mylitta. A collaborative programme has been initiated on identification of DNA markers linked to quantitative trait loci (QTLs) for cocoon weight and cocoon shell weight in B. mori. A network study on phylogeography of A. mylitta (tropical tasar) and A. Mylitta (muga) has been initiated. A genetic linkage map employing 518 simple sequence repeats or microsatellite markers in B. mori has been established. Under the Indian initiative on International Consortium on Lepidopteran Genome Project, about 35,000 ESTs from muga silkworm were generated. About 8200 unique putative genes from a redundant set of 35,000 ESTs were obtained. Work on testing of immunogenicity of silkworm m expressing PPRV-F and RPV-H protein through Bm NPV system in animals has been initiated. Stress-specific® based markers and SSR markers in mulberry have been developed.
Bioengineering programmes focussed on tissue engineering, biomaterials and medical devices, bioinstrumentation and biomedical sensors. The need for the devices and equipments for maternal, new born and child health care and indivenous production of sufactants for the treatment of premature babies has also been discussed. Network groups of clinicians and basic researchers are being formed in the identified areas. A separate task force considered programmes for development of biosensors; novel biomaterials; reconstruction of epidermal and dermal cells of skin, bioengineered cell sheet for corneal tissue engineering; rapid test for diagnosis of new born and childhood sepsis; biodegradable hydrogel for controlled drug delivery systems, etc.
(i) Human Genetics and Genome Analysis
Major infrastructure has been established to pursue post-geneomic research activities and to keep pace which international efforts to exploit the available human, animal and microbial genomics available in public domaJ1′ Several projects in the area of human genetics, human genome diversity, functional, structural, microbial biocomputing, pharmacogenomics, clinical proteomics were implemented involving large number of clinician – molecular geneticists and anthropologists. A strategy plan/roadmap document was prepared to initiate major human genetics and genomic network projects including genetic education in the country. A number of projects have also been supported on immuno-protemics based diagnostics of infectious diseases, clinical proteomics and RNAi. Programmes have also been generated on RNAi for the development of assays based on human cell as well as plants.
(j) Environmental Biotechnology
The Department organized a series of sectorial consultations with dyes, distilleries, refineries, paper and pulp pesticide manufacturing units to identify the problems in waste management and bottlenecks in treatment methods employed by them. The department has formulated a programme for recovery of critically endangered species in their natural habitat using biotechnological approaches. A programme on carbon sequestration using biotechnologicaltools. Support to R&D projects on industrial effluent treatment, restoration of degraded ecosystems, conservation and characterization of biodiversity using molecular tools is continuing. For leather, an environmentally friendly bioprocessing route as opposed to currently practiced, highly polluting chemical route-this would lead to a paradigm shift in age old leather processing.
(k) Biotechnology for Societal Development
The projects implemented could help in increasing the skills and income of SC/ST people, rural folk and women through product and process development and employment generation and improvement of their health status. Many people have been benefitted through ongoing projects on cultivation of aromatic and medicinal plants, mushroom, biological control of plant pests and diseases, biofuel, solid waste management, vermiculture and vermicomposting, biofertilizers, aquaculture, seaweed cultivation, poultry farming and human healthcare, etc.
(l) Biotechnology Parks and Incubators Apart from implementation of projects of Biotechnology Park at Lucknow, Uttar Pradesh and Biotechnology Incubation Centre at Shapoorji Pallonji Biotech Park, Hyderabad, Andhra Pradesh, four new projects were ap-proved for setting up of Biotech Incubation/Pilot Plant facilities at Punjab, Himachal Pradesh, Karnataka and Kerala. The Biotech Park at Lucknow is at advanced stage of implementation and building construction of BTIC at Hyderabad is progressing well.
(m) Government Initiatives on Biofuels
The government has approved the National Policy on Biofuels and the setting up of National Bio-fuel Coordination Committee and Bio-Fuel Steering Committee. Under the policy, by 2017, India will be increasing the blending of biofuels with petrol and diesel to 20 per cent.
The government has already initiated a project to conduct genome-wide research on a range of agronomically important crops.
Nanoelectronics Centres have been launched by the government, as a joint project of the Indian Institute of Science (IISc) Bangalore and Indian Institute of Technology, Bombay (IITB) with an investment of US$ 20.54 million.
The country gave its nod for commercial cultivation of BT cotton in early 2002. Growing manifold, within six years, the BT cotton acreage today accounts for about 70 per cent of the total area under cotton cultivation. Since then, agri-biotech continues to be the fastest growing industry among all the biotech industries in the country.
Recent Achievements in India
Some of developments in the recent times bear testimony to the robust growth momentum in Indian biotech industry:
v Biocon had found a place amongst top 20 global biotechnology companies. Biocon Limited was the only Asian company to feature in this ranking at number 20. The companies were ranked according to their revenue and income.
v Asia’s first and the world’s second human DNA bank has been set up at the Biotech Park in Uttar Pradesh’s Lucknow district. The members of the DNA bank will receive a microchip-based DNA card containing information of their fingerprints, and anthropological details.
v Biovet, an integrated biotechnology firm, launched Asia’s first Bio Safety Level-4 (BSL-4) manufacturing facility, specifically designed to facilitate product development and manufacturing of vaccines like Foot and Mouth Disease vaccine (FMD), in Malur, near Bangalore.
v A team of scientists, led by Indian American Suresh Subramani, is believed to have cracked a vital a biological puzzle that may hold the key to everything from ageing to cancer.